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Abstract
Malaria reduces host fitness and survival by pathogen-mediated damage and inflammation. Disease tolerance mechanisms counter these negative effects without decreasing pathogen load. Here, we demonstrate that in four different mouse models of malaria, adrenal hormones confer disease tolerance and protect against early death, independently of parasitemia. Surprisingly, adrenalectomy differentially affects malaria-induced inflammation by increasing circulating cytokines and inflammation in the brain but not in the liver or lung. Furthermore, without affecting the transcription of hepatic gluconeogenic enzymes, adrenalectomy causes exhaustion of hepatic glycogen and insulin-independent lethal hypoglycemia upon infection. This hypoglycemia is not prevented by glucose administration or TNF-alpha neutralization. In contrast, treatment with a synthetic glucocorticoid (dexamethasone) prevents the hypoglycemia, lowers cerebral cytokine expression and increases survival rates. Overall, we conclude that in malaria, adrenal hormones do not protect against lung and liver inflammation. Instead, they prevent excessive systemic and brain inflammation and severe hypoglycemia, thereby contributing to tolerance.
Keywords
:RESPIRATORY-DISTRESS-SYNDROME, SEVERE FALCIPARUM-MALARIA, GLUCOCORTICOID-RECEPTOR, PLASMODIUM-BERGHEI, CEREBRAL MALARIA, METABOLIC ADAPTATION, CONFERS TOLERANCE, LACTIC-ACIDOSIS, NEURONAL DEATH, MURINE MALARIA

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Citation

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MLA
Vandermosten, Leen, Thao-Thy Pham, Sofie Knoops, et al. “Adrenal Hormones Mediate Disease Tolerance in Malaria.” NATURE COMMUNICATIONS 9 (2018): n. pag. Print.
APA
Vandermosten, L., Pham, T.-T., Knoops, S., De Geest, C., Lays, N., Van der Molen, K., Kenyon, C. J., et al. (2018). Adrenal hormones mediate disease tolerance in malaria. NATURE COMMUNICATIONS, 9.
Chicago author-date
Vandermosten, Leen, Thao-Thy Pham, Sofie Knoops, Charlotte De Geest, Natacha Lays, Kristof Van der Molen, Christopher J Kenyon, et al. 2018. “Adrenal Hormones Mediate Disease Tolerance in Malaria.” Nature Communications 9.
Chicago author-date (all authors)
Vandermosten, Leen, Thao-Thy Pham, Sofie Knoops, Charlotte De Geest, Natacha Lays, Kristof Van der Molen, Christopher J Kenyon, Manu Verma, Karen E Chapman, Frans Schuit, Karolien De Bosscher, Ghislain Opdenakker, and Philippe E Van den Steen. 2018. “Adrenal Hormones Mediate Disease Tolerance in Malaria.” Nature Communications 9.
Vancouver
1.
Vandermosten L, Pham T-T, Knoops S, De Geest C, Lays N, Van der Molen K, et al. Adrenal hormones mediate disease tolerance in malaria. NATURE COMMUNICATIONS. 2018;9.
IEEE
[1]
L. Vandermosten et al., “Adrenal hormones mediate disease tolerance in malaria,” NATURE COMMUNICATIONS, vol. 9, 2018.
@article{8583244,
  abstract     = {Malaria reduces host fitness and survival by pathogen-mediated damage and inflammation. Disease tolerance mechanisms counter these negative effects without decreasing pathogen load. Here, we demonstrate that in four different mouse models of malaria, adrenal hormones confer disease tolerance and protect against early death, independently of parasitemia. Surprisingly, adrenalectomy differentially affects malaria-induced inflammation by increasing circulating cytokines and inflammation in the brain but not in the liver or lung. Furthermore, without affecting the transcription of hepatic gluconeogenic enzymes, adrenalectomy causes exhaustion of hepatic glycogen and insulin-independent lethal hypoglycemia upon infection. This hypoglycemia is not prevented by glucose administration or TNF-alpha neutralization. In contrast, treatment with a synthetic glucocorticoid (dexamethasone) prevents the hypoglycemia, lowers cerebral cytokine expression and increases survival rates. Overall, we conclude that in malaria, adrenal hormones do not protect against lung and liver inflammation. Instead, they prevent excessive systemic and brain inflammation and severe hypoglycemia, thereby contributing to tolerance.},
  articleno    = {4525},
  author       = {Vandermosten, Leen and Pham, Thao-Thy and Knoops, Sofie and De Geest, Charlotte and Lays, Natacha and Van der Molen, Kristof and Kenyon, Christopher J and Verma, Manu and Chapman, Karen E and Schuit, Frans and De Bosscher, Karolien and Opdenakker, Ghislain and Van den Steen, Philippe E},
  issn         = {2041-1723},
  journal      = {NATURE COMMUNICATIONS},
  keywords     = {:RESPIRATORY-DISTRESS-SYNDROME,SEVERE FALCIPARUM-MALARIA,GLUCOCORTICOID-RECEPTOR,PLASMODIUM-BERGHEI,CEREBRAL MALARIA,METABOLIC ADAPTATION,CONFERS TOLERANCE,LACTIC-ACIDOSIS,NEURONAL DEATH,MURINE MALARIA},
  language     = {eng},
  pages        = {18},
  title        = {Adrenal hormones mediate disease tolerance in malaria},
  url          = {http://dx.doi.org/10.1038/s41467-018-06986-5},
  volume       = {9},
  year         = {2018},
}

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